Folates

Abstract

Folic acid is a vitamin required for normal growth. It was discovered as a stable factor in extracts of yeast and of liver, which cured anaemia in pregnant women. The preponderant forms of folic acid in tissues are tetrahydrofolate polyglutamates with single carbon adducts corresponding to methanol, formaldehyde and formate. Folates are essential for the enzymatic oxidation, reduction and transfer of single carbon units involved in the metabolism of thymidylate, purine nucleotides, methionine, serine, histidine and choline.

Keywords: Folates; vitamins; metabolism

Figure 1.

Folic acid

Figure 2.

5,6,7,8‐Tetrahydrofolic acid R=H

Figure 3.

5,6,7,8‐Tetrahydrofolic acid poly‐γ‐glutamate

Figure 4.

The thymidylate cycle.

Figure 5.

(a) Formation of 5‐methyltetrahydrofolate catalysed by methylenetetrahydrofolate reductase. (b) Formation of methionine catalysed by cobalamin‐dependent methionine synthase.

Figure 6.

Folate‐dependent reactions in purine nucleotide biosynthesis.

Figure 7.

Folate antagonists.

Figure 8.

5,6,7,8‐Tetrahydrobiopterin.

Figure 9.

5,6,7,8‐Tetrahydromethanopterin.

close

References

Fu T‐F, Rife JP and Schirch V (2001) The role of serine hydroxymethyltransferase isozymes in one‐carbon metabolism in MCF‐7 cells as determined by 13C NMR. Archives in Biochemistry and Biophysics 393: 42–50.

Gonzalez JC, Banerjee RV, Huang S, Sumner JS and Matthews RG (1992) Comparison of cobalamin‐independent and cobalamin‐dependent methionine synthases from Esherichia coli‐2 solutions to the same chemical problem. Biochemistry 31: 6045–6056.

Herbert V (1968) Folic acid deficiency in man. Vitamins and Hormones 26: 525–538.

Kisliuk RL (1984) The biochemistry of folates. In: Sirotnak FM, Ensminger WD, Burchall JJ and Montgomery JA (eds) Folate Antagonists as Therapeutic Agents, vol. 1, pp. 1–55. New York: Academic Press.

Montserrat C, Anguera C, Suh J et al. (2003) Methenyltetrahydrofolate synthetase regulates folate turnover and accumulation. Journal of Biological Chemistry 278: 29856–29862.

Quinlivan EP, Roje S, Basset G et al. (2003) The folate precursor p‐aminobenzoate is reversibly converted to its glucose ester in the plant cytosol. Journal of Biological Chemistry 278: 20731–20737.

Rozen R (2002) Methylenetetrahydrofolate reductase: a link between folate and riboflavin?. American Journal of Clinical Nutrition 76: 301–302.

Shane B (1989) Folylpolyglutamate synthesis and role in the regulation of one‐carbon metabolism. Vitamins and Hormones 45: 263–335.

Shane B (2003) Folate fortification: enough already?. American Journal of Clinical Nutrition 77: 8–9.

Sirotnak FM and Tolner B (1999) Carrier‐mediated membrane transport of folates in mammalian cells. Annual Review of Nutrition 19: 91–122.

Stortchevoi A, Varshney U and RajBhandary UL (2003) Common location of determinants in initiator transfer RNAs for initiator–elongator discrimination in bacteria and eucaryotes. Journal of Biological Chemistry 278: 17672–17679.

Stover P and Schirch V (1993) The metabolic role of leucovorin. Trends in Biochemical Sciences 18: 102–106.

Thony B, Auerbach G and Blau N (2000) Tetrahydrobiopterin biosynthesis, regeneration and functions. Biochemical Journal 347(1): 1–16.

White R (2001) Biosynthesis of methanogenic cofactors. Vitamins and Hormones 61: 299–337.

Wolan DW, Greasley SE, Beardsley GP and Wilson IA (2002) Structural insights into the Avian AICAR transformylase mechanism. Biochemistry 41: 15505–15513.

Yeo EJ and Wagner C (1994) Tissue distribution of glycine N‐methyltransferase, a major folate‐binding protein of liver. Proceedings of the National Academy of Sciences of the USA 91: 210–214.

Further Reading

Blakley RL (1969) The Biochemistry of Folates and Related Pteridines, pp.1–569. New York: Wiley Interscience.

Blakley RL and Benkovic SJ (eds) (1984) Folates and Pterins, vol. 1, Chemistry and Biochemistry of Folates, pp. 1–628. New York: Wiley Interscience.

Cossins EA (2000) The fascinating world of folate and one‐carbon metabolism. Canadian Journal of Botany 78: 691–708.

Kisliuk RL (1999) The biochemistry of folates. In: Jackman A (ed.) Antifolate Drugs in Cancer Therapy, pp. 13–36. Totowa, NJ: Humana Press.

Stokstad ELR (1954) Pteroylglutamic acid. In: Sebrell WH Jr and Harris RS (eds) The Vitamins, vol. III, pp. 89–217. New York: Academic Press.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Kisliuk, Roy L(Apr 2006) Folates. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003924]